title: Innate immunity, through late complement components activation, contributes to the development of early vascular inflammation and morphologic alterations in experimental diabetes.
abstract: OBJECTIVE
  To verify if innate immunity, and namely the assembly of terminal complement complex (TCC) could be involved in the development of early diabetic vascular damage.
  
  
  RESULTS
  At first in 2 groups of diabetic or non-diabetic Wistar rats the occurrence of basal or stimulated stable adherence to the endothelial layer and extravasation of circulating fluorescently-labelled leukocytes was assessed by using an in vivo videomicroscopy technique. In a second part of the study, the development of vascular damage in short term diabetes was studied in the genetically C6 deficient rats of the PVG strain, and compared with those observed in the wild-type C6 sufficient animals. Here, the analysis of mesentery vascular expression of mRNA for vascular cell adhesion molecule (VCAM)-1, transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), and platelet-derived growth factor (PDGF), the evaluation of intravascular protein levels of VCAM-1, TGF-β, CTGF, proliferative cell nuclear antigen (PCNA), as well as the assessment of structural changes and Complement components deposition at the mesentery arterial vascular wall were also performed.
  
  
  CONCLUSIONS
  Leukocyte trafficking, mesentery arteries hypertrophy, extracellular matrix deposition, local vascular gene and protein expression of VCAM-1, TGF-β, CTGF and PCNA, as well as PGDF gene expression were all increased by short term diabetes, but all significantly reduced in the C6 deficient diabetic animals, thus suggesting an active role for TCC in the development of vascular inflammation in the early phases of experimental diabetes.
authors.affiliation: Department of Medical, Technological and Translational Sciences, University of Trieste, Italy. f.fischetti@fmc.units.it
authors.forename: F
authors.initials: F
authors.lastname: Fischetti
authors.forename: R
authors.initials: R
authors.lastname: Candido
authors.forename: B
authors.initials: B
authors.lastname: Toffoli
authors.forename: P
authors.initials: P
authors.lastname: Durigutto
authors.forename: S
authors.initials: S
authors.lastname: Bernardi
authors.forename: R
authors.initials: R
authors.lastname: Carretta
authors.forename: F
authors.initials: F
authors.lastname: Tedesco
authors.forename: B
authors.initials: B
authors.lastname: Fabris
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure; D003167:Complement Activation / Q000235:genetics; D003176:Complement C3 / Q000378:metabolism; D003183:Complement C6 / Q000172:deficiency / Q000235:genetics; D003186:Complement C9 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000235:genetics / Q000378:metabolism*; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006984:Hypertrophy; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D036904:Leukocyte Rolling; D008297:Male; D008638:Mesenteric Arteries / Q000276:immunology / Q000473:pathology; D018715:Microscopy, Video; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C526316:CCN2 protein, rat; D003176:Complement C3; D003183:Complement C6; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D018836:Inflammation Mediators; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; D055513:Connective Tissue Growth Factor